It is frequently necessary to store moisture sensitive materials for relatively long periods in containers. In a particular example, certain pharmaceutical substances are supplied and/or stored in small vials containing one or more unit doses of the dry substance. Such vials are normally sealed with an elastomeric closure including a closure wall across the mouth, and having a puncturable region such as a thin part of the closure wall through which a hypodermic needle may be inserted. By means of such a needle water or other suitable aqueous medium may be injected into the vial, the substance dissolved in situ, and the solution then withdrawn via the needle into a syringe for use in the short term before significant hydrolysis of the moisture sensitive material occurs. Such an elastomeric closure is often retained on the mouth opening of the vial by a thin metal circlip. Such puncturable seals enable this operation to be sterile. During storage the presence of atmospheric moisture within the container, or the ingress of atmospheric moisture, can cause decomposition of such materials
Often moisture sensitive pharmaceutical substances are provided in containers together with an internal desiccant in the container, for example a small sachet of molecular sieve or silica gel. Clearly this is not practical when the substance has to be made up in situ within the container as described above, as contamination by desiccant on dissolution of the substance is likely.
It is known to compound polymeric materials with desiccants for various applications, but mostly as moisture absorbing spacers for multiple glazing panels. For example U.S. Pat. No. 4,485,204 and U.S. Pat. No. 4,547,536 disclose blends of polyester or polyester plus a butadiene polymer, plus a desiccant such as calcium oxide. EP 0599690 discloses a blend of a polymer such as styrene butadiene rubber, plus molecular sieve, plus also a fibrous material. EP 0599690 suggests the general possibility of use of such a polymer for drying of moisture sensitive pharmaceuticals, giving results for moisture absorption at 80% RH.
An example of a moisture sensitive pharmaceutical substance is clavulanic acid and its salts, such as potassium clavulanate. Potassium clavulanate is both hygroscopic and readily hydrolysed by water, so for handling and long term storage of potassium clavulanate it is necessary for the immediate environment to be kept extremely dry, e.g. 30% Relative Humidity ("RH") or less, preferably 10% RH or less, ideally as low as possible. To obtain and maintain such conditions in a container such as a vial of the type mentioned above requires quite a powerful desiccant ability.
Potassium clavulanate is a beta-lactamase inhibitor, and is often provided in a formulation in combination with a partner beta-lactam antibiotic. A partner which is often used in such formulations is amoxycillin. For injectable formulations amoxycillin is used in the form of sodium amoxycillin. In some forms sodium amoxycillin is a powerful desiccant, and when contained together with potassium clavulanate in a sealed vial such forms of sodium amoxycillin can exert a dehydrating effect which helps to preserve the potassium clavulanate. Other forms of sodium amoxycillin, such as the anhydrous crystalline form disclosed in EP 0131147 are less desiccating, and although it would be desirable to use such forms in formulations together with potassium clavulanate, the problem arises that these forms can be insufficiently desiccating to protect the potassium clavulanate from hydrolysis resulting from traces of moisture in the vial.